1. Field of the Invention
The present invention relates to mass spectrometry systems. More particularly, it relates to mass spectrometry systems that are useful for the determination of elemental compositions or isotope distributions, including for large organic molecules such as proteins or peptides, environmental pollutants, pharmaceuticals and their metabolites, and petrochemical compounds, to methods of analysis used therein, and to a computer program product having computer code embodied therein for causing a computer, or a computer and a mass spectrometer in combination, to affect such determination.
2. Prior Art
It has been generally accepted by those skilled in the art that the determination of elemental composition using mass spectrometry requires high mass accuracy, which can only be expected from a higher resolution system, typically a qTOF, FTMS, or a similar system such as the newly introduced OrbiTrap system manufactured by Thermo Electron Corporation of Waltham, Mass., USA. The rationale behind high mass accuracy for the purpose of elemental composition determination is well established in the field. For example, an elemental composition search with C (0-50), H (0-100), N (0-5), O (0-10), S (0-2), P (0-3), and Na (0-1) in a small mass tolerance window of +/−0.002 Da for a small molecule compound at an accurately measured mass of 399.1806 Da will result in only about 15 possible formulas, a manageable list from which to narrow down and determine the correct elemental composition. More generally, it has been found that 5 ppm mass error would allow for the easy determination of elemental composition from small molecule drugs or metabolites to large molecule proteins or peptides.
In the crossed referenced patents and applications, such as U.S. Pat. No. 6,983,213, it has been shown that an extensive mass spectral calibration involving both mass and peak shape function can achieve high mass accuracy on even a unit mass resolution system, making elemental composition determination feasible on routine mass spectrometry systems. Furthermore, the advantages of performing elemental composition search using (preferably fully calibrated) profile mode mass spectral data have also been disclosed in the above cross referenced applications, particularly in International Patent Application PCT/US2004/013096, filed on Apr. 28, 2004; U.S. patent application Ser. No. 11/261,440, filed on Oct. 28, 2005; International Patent Application PCT/US2005/039186, filed on Oct. 28, 2005.
With both the accurate mass and the profile fitting information available, the list of candidate formulas from the elemental composition search can be ranked or scored based on either the mass error or the profile fitting error, creating some level of confusion.
In addition, as an important niche application of mass spectrometry, the measurement of isotope ratios is of key importance in many applications, including geology, identification of the source of origins for agricultural products, or even clinical diagnostics such as the determination of H-Pylori through breath CO2 analysis. This is typically achieved on dedicated high resolution mass spectrometers such as magnetic sector instruments and referred to as the isotope ratio mass spectrometry or IRMS, after chemical derivatization of the target compound into a more measurable form such as CO2.